Clinical and Laboratory Associations with Methotrexate Metabolism Gene Polymorphisms in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that causes loss of joint function and significantly reduces quality of life. Plasma metabolite concentrations of disease-modifying anti-rheumatic drugs (DMARDs) can influence treatment efficacy and toxicity. This study explored the relationship between DMARD-metabolising gene variants and plasma metabolite levels in RA patients. DMARD metabolite concentrations were determined by tandem mass-spectrometry in plasma samples from 100 RA patients with actively flaring disease collected at two intervals. Taqman probes were used to discriminate single-nucleotide polymorphism (SNP) genotypes in cohort genomic DNA: rs246240 (ABCC1), rs1476413 (MTHFR), rs2231142 (ABCG2), rs3740065 (ABCC2), rs4149081 (SLCO1B1), rs4846051 (MTHFR), rs10280623 (ABCB1), rs16853826 (ATIC), rs17421511 (MTHFR) and rs717620 (ABCC2). Mean plasma concentrations of methotrexate (MTX) and MTX-7-OH metabolites were higher (p < 0.05) at baseline in rs4149081 GA genotype patients. Patients with rs1476413 SNP TT or CT alleles have significantly higher (p < 0.001) plasma poly-glutamate metabolites at both study time points and correspondingly elevated disease activity scores. Patients with the rs17421511 SNP AA allele reported significantly lower pain scores (p < 0.05) at both study intervals. Genotyping strategies could help prioritise treatments to RA patients most likely to gain clinical benefit whilst minimizing toxicity

A Measurement of Time-Averaged Aerosol Optical Depth using Air-Showers Observed in Stereo by HiRes

Air fluorescence measurements of cosmic ray energy must be corrected for attenuation of the atmosphere. In this paper we show that the air-showers themselves can yield a measurement of the aerosol attenuation in terms of optical depth, time-averaged over extended periods. Although the technique lacks statistical power to make the critical hourly measurements that only specialized active instruments can achieve, we note the technique does not depend on absolute calibration of the detector hardware, and requires no additional equipment beyond the fluorescence detectors that observe the air showers. This paper describes the technique, and presents results based on analysis of 1258 air-showers observed in stereo by the High Resolution Fly's Eye over a four year span.Comment: 7 pages, 3 figures, accepted for publication by Astroparticle Physics Journa

Observation of the Ankle and Evidence for a High-Energy Break in the Cosmic Ray Spectrum

We have measured the cosmic ray spectrum at energies above $10^{17}$ eV using the two air fluorescence detectors of the High Resolution Fly's Eye experiment operating in monocular mode. We describe the detector, PMT and atmospheric calibrations, and the analysis techniques for the two detectors. We fit the spectrum to models describing galactic and extragalactic sources. Our measured spectrum gives an observation of a feature known as the ``ankle'' near $3\times 10^{18}$ eV, and strong evidence for a suppression near $6\times 10^{19}$ eV.Comment: 14 pages, 9 figures. To appear in Physics Letters B. Accepted versio

Energy and Flux Measurements of Ultra-High Energy Cosmic Rays Observed During the First ANITA Flight

The first flight of the Antarctic Impulsive Transient Antenna (ANITA) experiment recorded 16 radio signals that were emitted by cosmic-ray induced air showers. For 14 of these events, this radiation was reflected from the ice. The dominant contribution to the radiation from the deflection of positrons and electrons in the geomagnetic field, which is beamed in the direction of motion of the air shower. This radiation is reflected from the ice and subsequently detected by the ANITA experiment at a flight altitude of 36km. In this paper, we estimate the energy of the 14 individual events and find that the mean energy of the cosmic-ray sample is 2.9 EeV. By simulating the ANITA flight, we calculate its exposure for ultra-high energy cosmic rays. We estimate for the first time the cosmic-ray flux derived only from radio observations. In addition, we find that the Monte Carlo simulation of the ANITA data set is in agreement with the total number of observed events and with the properties of those events.Comment: Added more explanation of the experimental setup and textual improvement

A Likelihood Method for Measuring the Ultrahigh Energy Cosmic Ray Composition

Air fluorescence detectors traditionally determine the dominant chemical composit ion of the ultrahigh energy cosmic ray flux by comparing the averaged slant depth of the shower maximum, $X_{max}$, as a function of energy to the slant depths expect ed for various hypothesized primaries. In this paper, we present a method to make a direct measurement of the expected mean number of protons and iron by comparing the shap es of the expected $X_{max}$ distributions to the distribution for data. The advantages of this method includes the use of information of the full distribution and its ability to calculate a flux for various cosmic ray compositi ons. The same method can be expanded to marginalize uncertainties due to choice of spectra, hadronic models and atmospheric parameters. We demonstrate the technique with independent simulated data samples from a parent sample of protons and iron. We accurately predict the number of protons and iron in the parent sample and show that the uncertainties are meaningful.Comment: 11 figures, 22 pages, accepted by Astroparticle Physic

Alternative Methods to Finding Patterns in HiRes Stereo Data

In this paper Ultra High Energy Cosmic Rays UHECRs data observed by the HiRes fluorescence detector in stereo mode is analyzed to search for events in the sky with an arrival direction lying on a great circle. Such structure is known as the arc structure. The arc structure is expected when the charged cosmic rays pass through the galactic magnetic field. The arcs searched for could represent a broad or a small scale anisotropy depending on the proposed source model for the UHECRs. The Arcs in this paper are looked for using Hough transform were Hough transform is a technique used to looking for patterns in images. No statistically significant arcs were found in this study

The Antarctic Impulsive Transient Antenna Ultra-high Energy Neutrino Detector Design, Performance, and Sensitivity for 2006-2007 Balloon Flight

We present a detailed report on the experimental details of the Antarctic Impulsive Transient Antenna (ANITA) long duration balloon payload, including the design philosophy and realization, physics simulations, performance of the instrument during its first Antarctic flight completed in January of 2007, and expectations for the limiting neutrino detection sensitivity. Neutrino physics results will be reported separately.Comment: 50 pages, 49 figures, in preparation for PR

Reproducibility in the absence of selective reporting : An illustration from large-scale brain asymmetry research

Altres ajuts: Max Planck Society (Germany).The problem of poor reproducibility of scientific findings has received much attention over recent years, in a variety of fields including psychology and neuroscience. The problem has been partly attributed to publication bias and unwanted practices such as p-hacking. Low statistical power in individual studies is also understood to be an important factor. In a recent multisite collaborative study, we mapped brain anatomical left-right asymmetries for regional measures of surface area and cortical thickness, in 99 MRI datasets from around the world, for a total of over 17,000 participants. In the present study, we revisited these hemispheric effects from the perspective of reproducibility. Within each dataset, we considered that an effect had been reproduced when it matched the meta-analytic effect from the 98 other datasets, in terms of effect direction and significance threshold. In this sense, the results within each dataset were viewed as coming from separate studies in an "ideal publishing environment," that is, free from selective reporting and p hacking. We found an average reproducibility rate of 63.2% (SD = 22.9%, min = 22.2%, max = 97.0%). As expected, reproducibility was higher for larger effects and in larger datasets. Reproducibility was not obviously related to the age of participants, scanner field strength, FreeSurfer software version, cortical regional measurement reliability, or regional size. These findings constitute an empirical illustration of reproducibility in the absence of publication bias or p hacking, when assessing realistic biological effects in heterogeneous neuroscience data, and given typically-used sample sizes